RELATIONSHIP BETWEEN LIPID METABOLISM AND INSULIN-MEDIATED GLUCOSE DISPOSAL

脂质代谢与胰岛素介导的葡萄糖代谢之间的关系

• 批准号: 4690049
• 负责人: B V HOWARD
• 金额: --
• 依托单位: NAT INST OF ARTHRITIS, DIABETES, DIGESTIVE & KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4690049
• 关键词: adipocytes; biopsy; calorimetry; epidemiology; free fatty acids; glucose metabolism; hormone regulation /control mechanism; human subject; insulin; lipid metabolism; nutrition related tag; obesity; oxidation; radiotracer; tissue /cell culture

It is well known that the availability of fatty acids for oxidation at the cellular level might be responsible for alterations in carbohydrate metabolism. While some studies have shown that changes in free fatty acid concentrations are accompanied by reciprocal changes in whole body glucose oxidation, it is not clear whether total insulin mediated glucose disposal may be correlated to changes in metabolism. This study combines the techniques of the euglycemic clamp, indirect calorimetry, and labeled free fatty acid technique to determine the relationship between insulin mediated glucose disposal, glucose oxidation and storage and measures of lipid metabolism. In vitro adipocyte data is collected from adipocytes isolated by open abdominal fat biopsy from the same subjects. Subjects are studied over a range of obesity to provide a range of lipid metabolic profiles and insulin resistance. The results suggest a direct interaction between lipid oxidation and glucose oxidation in vivo. However, this interrelationship can only partially explain impaired in vivo insulin mediated glucose disposal, since the former decreases per gm of fat as obesity increases whereas the latter increases. This implies that several neurologic or hormonal factors may interact to regulate FFA release from adipose tissue in obese individuals. Finally, a large non-oxidative component of FFA turnover has been observed which far exceeds the rate of VLDL triglyceride production. This component may be important in the regulation of FFA metabolism in vivo.

众所周知，脂肪酸在氧化反应中的可用性取决于温度。 细胞水平可能负责改变碳水化合物 新陈代谢. 虽然一些研究表明游离脂肪酸的变化 浓度伴随着全身葡萄糖的相互变化 氧化，尚不清楚是否总胰岛素介导的葡萄糖处置 可能与新陈代谢的变化有关。 这项研究结合了 正葡萄糖钳夹技术、间接量热法和标记游离 脂肪酸技术，以确定胰岛素介导的 葡萄糖的处理、葡萄糖的氧化和储存以及脂质的测量 新陈代谢. 从分离的脂肪细胞收集体外脂肪细胞数据 通过腹部脂肪活检 研究对象 以提供一系列脂质代谢谱， 胰岛素抵抗 结果表明，脂质之间的直接相互作用 氧化和葡萄糖氧化。 然而，这种相互关系 只能部分解释体内胰岛素介导的葡萄糖受损 处置，因为前者减少每克脂肪肥胖增加 而后者增加。 这意味着一些神经系统或 激素因子可能相互作用，调节脂肪组织FFA的释放 在肥胖个体中。 最后，FFA的大量非氧化成分 已观察到的周转率远远超过极低密度脂蛋白甘油三酯 生产 该组分在FFA的调节中可能是重要的。 体内代谢